Methods and compositions relating to HPV-associated pre-cancerous and cancerous growths, including CIN

Abstract

The present invention concerns the use of E6 and/or E7 peptides from human papilloma virus (HPV) to evaluate a cell-mediated response in a patient infected with HPV to determine the prognosis for that patient with respect to the development or recurrence of pre-cancerous or cancerous growths, including cervical intraepithelial neoplasia (CIN).

1. A method for reducing the risk of recurrence of a pre-cancerous or cancerous growth in a patient infected with HPV who has been treated for the growth comprising
 administering to a patient at risk for recurrence of HPV-associated pre-cancerous or cancerous growth an effective amount of at least one E6 or E7 HPV peptide, wherein a cell-mediated immune response to at least one E6 or E7 peptide is induced in the patient and the cell-mediated immune response to such at least one peptide is indicative of a reduced risk of recurrence. 
 
     
     
       2. The method of  claim 1 , wherein the patient is administered an effective amount of an E6 HPV peptide. 
     
     
       3. The method of  claim 2 , wherein the E6 peptide is K9L (SEQ ID NO:1), E10I (SEQ ID NO:2), C10R (SEQ ID NO:3), Q15L (SEQ ID NO:4), V10C (SEQ ID NO:5), P9L (SEQ ID NO:6), P10I (SEQ ID NO:7), Q20P (SEQ ID NO:8), R16R (SEQ ID NO:9), or G10S (SEQ ID NO:10). 
     
     
       4. The method of  claim 2 , wherein the patient is administered a combination of E6 HPV peptides selected from the group consisting of K9L (SEQ ID NO: 1), E10I (SEQ ID NO:2), C10R (SEQ ID NO:3), Q15L (SEQ ID NO:4), and V10C (SEQ ID NO:5). 
     
     
       5. The method of  claim 1 , wherein the patient is administered an effective amount of an E7 HPV peptide. 
     
     
       6. The method of  claim 5 , wherein the E7 HPV peptide is T10Q (SEQ ID NO:11), M9T (SEQ ID NO:12), D9L (SEQ ID NO:13), Q19D (SEQ ID NO:14), R9F (SEQ ID NO:15 ), R9V (SEQ ID NO:16), L9V (SEQ ID NO:17), G10C (SEQ ID NO:18), or D20C (SEQ ID NO:19). 
     
     
       7. The method of  claim 5 , wherein the patient is administered a combination of E7 HPV peptides selected from the group consisting of T10Q (SEQ ID NO:11), M9T (SEQ ID NO:12), D9L (SEQ ID NO:13), Q19D (SEQ ID NO:14), R9F (SEQ ID NO:15), R9V (SEQ ID NO:16), L9V (SEQ ID NO:17), G10C (SEQ ID NO:18), and D20C (SEQ ID NO:19). 
     
     
       8. The method of  claim 1 , wherein the patient is administered at least one E6 HPV peptide and at least one E7 HPV peptide. 
     
     
       9. The method of  claim 1 , wherein the patient has a history of a pre-cancerous growth. 
     
     
       10. The method of  claim 9 , wherein the pre-cancerous growth is cervical intraepithelial neoplasia (CIN). 
     
     
       11. The method of  claim 1 , wherein the patient has a history of a cancerous growth. 
     
     
       12. The method of  claim 11 , wherein the patient has a history of cervical cancer. 
     
     
       13. The method of  claim 1 , wherein the patient has undergone ablative treatment of a pre-cancerous or cancerous growth in the genitourinary tract. 
     
     
       14. The method of  claim 13 , wherein the ablative treatment is selected from the group consisting of chemotherapy, radiotherapy, hormonal therapy, gene therapy, surgery, gene therapy, and immunotherapy. 
     
     
       15. The method of  claim 1 , wherein the at least one E6 or E7 HPV peptides are comprised in a pharmaceutical composition. 
     
     
       16. The method of  claim 15 , wherein the pharmaceutical composition further comprises an adjuvant. 
     
     
       17. The method of  claim 15 , wherein the pharmaceutical composition further comprises a lipid. 
     
     
       18. The method of  claim 17 , wherein the lipid is a phosphatidylglycerol, a phosphatidylcholine, a phosphatidylserine, a phosphatidylethanolamine, a sphingolipid, a cerebroside, or a ganglioside. 
     
     
       19. The method of  claim 18 , wherein the lipid is a phosphatidylglycerol. 
     
     
       20. The method of  claim 19 , wherein the phosphatidylglycerol is diacylphosphatidyglycerol. 
     
     
       21. The method of  claim 1 , wherein identifying a patient at risk for recurrence of HPV-associated pre-cancerous or cancerous growth comprises performing a Pap Smear test. 
     
     
       22. The method of  claim 1 , wherein identifying a patient at risk for recurrence of HPV-associated pre-cancerous or cancerous growth comprises performing colposcopy on the subject. 
     
     
       23. The method of  claim 1 , wherein administering to the patient an effective amount of at least one E6 or E7 HPV peptide comprises administering to the patient an expression construct comprising a nucleic acid sequence coding for at least one E6 or E7 HPV peptide wherein the nucleic acid sequence is under the transcriptional control of a promoter. 
     
     
       24. The method of  claim 23 , wherein the expression construct is comprised in a viral vector. 
     
     
       25. The method of  claim 24 , wherein the viral vector is a retroviral vector, an adenoviral vector, an adeno-associated viral vector, a vaccinia virus vector, or a herpes virus vector. 
     
     
       26. The method of  claim 23 , wherein the expression construct is comprised in a liposome. 
     
     
       27. The method of  claim 1 , wherein the at least one E6 or E7 HPV peptide is administered intravenously, intradermally, intraarterially, intraperitoneally, intralesionally, intravaginally, rectally, topically, intratumorally, intramuscularly, subcutaneously, mucosally, orally, or topically.